2007 Fiscal Year Final Research Report Summary
Basic and Clinical study on endocrine therapy of gynecologic diseases targeting aromatase
| Project/Area Number |
16209049
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Chiba University (2005-2007)
Kanazawa University (2004) |
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Principal Investigator |
SHOZU Makio Chiba University, Department of Reproductive Medicine, Professor (30226302)
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| Co-Investigator(Kenkyū-buntansha) |
INOUE Masaki Kanazawa University, Graduate School of Medical Science, Department of Obstetrics and Gynecology, Professor (10127186)
MITSUHASHI Akira Graduate School of Medicine, Chiba University, Department of Reproductive Medicine, Lecture (40302541)
USUI Hirokazu Graduate School of Medicine, Chiba University, Department of Reproductive Medicine, Associate Professor (90375634)
KIHARA Maki Chiba University Hospital, Department of Gynecology, Assistant Professor (20375760)
MURAKAMI Koichi Kanazawa University, Graduate School of Medical Science, Department of Obstetrics and Gynecology, Associate Professor (20242555)
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| Project Period (FY) |
2004 – 2007
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| Keywords | aromatase / inhibitor / uterine leiomyoma / endometriosis / ovulation induction |
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| Research Abstract |
Estrogen-dependent gynecologic diseases such as endometriosis, uterine leiomyoma and adenomyosis has been increased and worsened with a recent trend to late- or un-marriage in life. The older women become, the more difficult she ovulate. We have shown that an aromatase inhibitor(s) is a theoretical molecular target of endocrine therapy of these estrogen-dependent diseases as well as a specific ovulatory failure (PCOS). Here we examined therapeutic mechanisms of an aromatase inhibitor and showed the possible clinical usefulness of an aromatase inhibitor for management of the situations described earlier. In leiomyoma cells, enhanced expression of aromatase increased in situ estrogen, which possibly promoted the proliferation of their own. Absent activation of MAPK pathway in leiomyoma cells also contributed to enhanced cell proliferation through the reduction in Egr-1, resulting in low Rb expression. IGF-1 enhanced accumulation of aromatase in leiomyoma cells by deprivation of trafficking newly synthesized aromatase into lysosome, probably mediated by IGF-1 action on mTOR. There was a racial difference in aromatase expression of leiomyoma cells. It was shown that local application of a drug delivery system composed of fadrozole- or danazole-loaded hyaluronic acid successfully treated rat chocolate cyst model without systemic effect. Fadrozole was preoperatively administered to leiomyoma patients, who gave their consent for the study. Two third of patients showed reduction in volume by 25% with an improvement of symptoms, within the first 4 weeks. Another inhibitor of aromatase, letrozole, was administered to PCOS patients with an informed consent and found the letrozole was as effective as clomiphene in terms of ovulation induction and might be more beneficial to patients with implantation difficulty compared to clomiphene.
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Research Products
(98 results)
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[Journal Article] 子宮とアロマターゼ2008
Author(s)
可西直之, 生水真紀夫, 野村一人, 井上正樹
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Journal Title
HORMONE FRONTIER IN GYNECOLOGY 15・1
Pages: 28-32
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Regional rearrangements in chromosome 15q21 cause formation of cryptic promoters for the CYP19 (aromatase) gene.2007
Author(s)
Demura M, Martin RM, Shozu M, Sebastian S, Takayama K, Hsu WT, Schultz RA, Neely K, Bryant M, Mendonca BB, Hanaki K, Kanzaki S, Rhoads DB, Misra M, Bulun SE.
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Journal Title
Hum Mol Genet. 16・21
Pages: 2529-41
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Regional rearrangements in chromosome 15q21 cause formation of cryptic promoters for the CYP19 (aromatase) gene.2007
Author(s)
Demura M, Martin RM, Shozu M, Sebastian S, Takayama K, Hsu WT, Schultz RA, Neely K, Bryant M, Mendonca BB, Hanaki K, Kanzaki S, Rhoads DB, Misra M, Bulun SE.
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Journal Title
Hum Mol Genet. 16(21) (Epub 2007Jun21)
Pages: 2529-41
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Colonization by Clostridium difficile of neonates in a hospital, and infants and children in three day-care facilities of Kanazawa, Japan.2005
Author(s)
Matsuki S, Ozaki E, Shozu M, Inoue M, Shimizu S, Yamaguchi N, Karasawa T, Yamagishi T, Nakamura S.
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Journal Title
Int Microbiol. 8・1
Pages: 43-8
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Colonization by Clostridium difficile of neonates in a hospital, and infants and children in three day-care facilities of Kanazawa, Japan.2005
Author(s)
Matsuki S, Ozaki E, Shozu M, Inoue M, Shimizu S, Yamaguchi N, Karasawa T, Yamagishi T, Nakamura S.
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Journal Title
Int Microbiol. 8(1)
Pages: 43-8
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Aromatase inhibitor.2004
Author(s)
Shozu M, Murakami H, Nomura K, Shinohara K, Kasai T, Inoue M.
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Journal Title
New therapeutic approach for endometriosis. 25
Pages: 50-55
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Expression of Egr-1, a tumor suppressor gene, is consistently dow-regulated in leiomyomas of the uterus.2004
Author(s)
Ishikawa H, Shozu M, Murakami K, Minami M, Nomura K, Shinohara K, Kasai K, Segawa T, Inoue M.
Organizer
The Endocrine Society's 86th Meeting
Place of Presentation
New Orleans
Year and Date
20040000
Description
「研究成果報告書概要(和文)」より
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[Presentation] Insulin-like growth factor-1 modulates Aromatase synthesis in THP-1 cells.2004
Author(s)
Zhang Bo, Shozu M, Okada M, Inukai M, Murakami K, Kasai T, Shinohara K, Nomura L, Kato K, Minami N, Inoue M
Organizer
The 7th International Aromatase Conference
Place of Presentation
Edinburgh
Year and Date
20040000
Description
「研究成果報告書概要(和文)」より
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[Presentation] Expression of Egr-1, a tumor suppressor gene, is consistently down-regulated in leiomyomas of the uterus2004
Author(s)
Ishikawa H, Shozu M, Murakami K, Minami M, Nomura K, Shinohara K, Kasai K, Segawa T, Inoue M.
Organizer
The Endocrine Society's 86th Meeting
Place of Presentation
New Orleans
Year and Date
20040000
Description
「研究成果報告書概要(欧文)」より
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